This is a proposal to continue our case-control studies investigating the role of human papillomaviruses (HPV) in the development of anogenital cancers. The study will be conducted primarily in three counties of Western Washington that are covered by the population-based Cancer Surveillance System (CSS), a tumor registry that participates in the Surveillance Epidemiology and End Results Program (SEER) of the National Cancer Institute, and in Vancouver, British Columbia. (Penile, urethral, and vaginal cancers from ten additional counties will be included to provide a sufficient sample size.) All men and women aged 18-74 with one of six malignancies will be identified and invited to participate, and we estimate the following number of cases will be successfully interviewed: Invasive cancer of the cervix (448 cases); anal and perianal cancer (143 cases); vulvar cancer (102 cases); penile cancer (78 cases); urethral cancer (30 cases); and cancer of the vagina (60 cases). Eligible subjects will be all individuals with a diagnosis of one of these six cancers during a five-year period from April 1991 to March 1996. Cases and appropriate controls will be interviewed regarding a history of sexually-transmitted diseases, as well as other known risk factors for each specific site. Tissue specimens from surgery will be obtained from all cases and from women biopsied for certain benign vulvar conditions. Pap smears taken prior to diagnosis will be collected from women with cervical, vaginal, urethral, and vulvar cancer and the female population controls. Tissue and cytologic samples will be probed for evidence of human papillomavirus using molecular hybridization techniques. Blood samples will be collected for all cases and controls and analyzed for evidence of prior exposure to herpes simplex virus type 2 and for several types of HPV using currently available tests. Additional sera will be frozen for future determination of HPV antibodies as new and/or more sensitive serologic tests are developed for HPV.